Normal gut microbes make significant contributions to the overall health of their host including protection against harmful microorganisms and stimulation of the immune system. Their importance can be traced back to 400 B.C., as the ancient Greek physician Hippocrates wrote, “death sits in the bowels” and “bad digestion is the root of all evil”. The intestinal tract is the primary site of interaction between the host immune system and the microbial ecosystem. The microbiome contains at least 100-fold more genes than the complete human genome, and the composition of gut microflora can likely be altered due to the plasticity of the microbiome. In healthy individuals, alterations in the microbiome composition have been linked to dietary patterns, ageing, environment and host genotype, etc. Besides the genomic influence, the host's dietary and drug uptake can also alter the composition of microflora. The fat or carbohydrate-restricted low calorie diet made obese people lose weight and result in an increase in Bacteroidetes. Conversely, the microbes can influence the energy harvesting from diet. Furthermore, the gut microbiota can also affect the bioavailability and bioactivity of ingested products, including functional foods and traditional Chinese medicine (TCM). Recent findings have revealed that the gut microflora play an even greater role in modulating human metabolic phenotypes and individuals' drug responses than previously believed. For example in Ley R E, Turnbaugh P J, Klein S, Gordon J I (2006). Microbial ecology: human gut microbes associated with obesity. Nature 444: 1022-1023 and Nicholson J K, Holmes E, Wilson I D (2005). Gut microorganisms, mammalian metabolism and personalized health care. Nat Rev Microbiol 3: 431-438, the host's dietary and drug uptake can alter the microbial composition. Conversely, microbes can influence the bioavailability and bioactivity of ingested products, including functional foods and herbal medicines. For example, recent findings in Ley R E, Turnbaugh P J, Klein S, Gordon J I (2006). Microbial ecology: human gut microbes associated with obesity. Nature 444: 1022-1023 and Ley R E, Turnbaugh P J, Klein S, Gordon J I (2006). Microbial ecology: human gut microbes associated with obesity. Nature 444: 1022-1023 indicated that the composition of two predominant gut bacterial phylum, Firmicutes and Bacteroidetes, show tight association with obesity of human and mice.
Another recent report, namely, Holmes E, Loo R L, Stamler J, Bictash M, Yap I K, Chan Q et al., (2008). Human metabolic phenotype diversity and its association with diet and blood pressure. Nature 453: 396-400, on the metabolic phenotyping of urine specimens of 4,630 participants from China, Japan, UK and USA indicated that gut microbial activities contribute to the ethnic diversity and its association with diet and blood pressure. Studies also showed that gut microbiota can alter bioavailability of intake natural products. For example, in Akao T, Kawabata K, Yanagisawa E, Ishihara K, Mizuhara Y, Wakui Y et al., (2000). Baicalin, the predominant flavone glucuronide of scutellariae radix, is absorbed from the rat gastrointestinal tract as the aglycone and restored to its original form. The Journal of pharmacy and pharmacology 52: 1563-1568, the case of the flavones baicalin isolated from scutellariae radix, the ingested baicalin is first hydrolyzed by the gut microbacteria to form the aglycone, followed by absorption and subsequently conjugated back to baicalin. Another example in Wang Y, Tang H, Nicholson J K, Hylands P J, Sampson J, Holmes E (2005). A metabonomic strategy for the detection of the metabolic effects of chamomile (Matricaria recutita L.) ingestion. Journal of agricultural and food chemistry 53: 191-196, showed that functional food chamomile tea altered the metabolites and bacterial composition.
Metabolic activation of ginseng saponins and ginsenosides by intestinal bacteria has also been investigated extensively. Other natural products isolated from TCM have also been proven to be metabolized by gut microbes to form active drugs, such as glycyrrhizin, paeoniflorin, baicalin, puerarin and daidzin. Nevertheless, studies have been confined to the metabolites of the TCM, and no systematic study of the alteration of the microflora under the influence of ingested herbal medicines.
It is possible that TCM with a longer residence time in the intestinal tract may have a great chance to affect the gut microbial ecosystem. Saponins are the natural triterpenoids found in many herbal and edible plants. Saponins have the following traits underlying poor membrane permeability and result in poor intestinal absorption, relative high molecular mass (>500 Da), high hydrogen-bonding capacity (>12) and high molecular flexibility (>10). These non-absorbable saponins are too difficult to be absorbed through the intestinal wall and able to interact with gut microflora for a longer time. Saponins are commonly found in a large number of natural sources and particularly abundant in many herbal and edible plants. They are a group of amphiphilic glycosides containing one or more sugar chains bound to a nonpolar triterpene (FIG. 1A) or steroid aglycone (FIG. 1B) skeleton.
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